The clinonorm is not used for contraception.
If contraception is necessary, non-hormonal methods should be used (with the exception of calendar and temperature methods). If you suspect a pregnancy, you should stop taking the pills until pregnancy is not ruled out (see "Pregnancy and lactation").
In the presence or deterioration of any of the following conditions or risk factors, the relationship between individual risk and benefit of treatment should be evaluated before starting or continuing HRT.
Venous thromboembolism
In a number of controlled randomized, and wage epidemiological studies, an increased relative risk of venous thromboembolism (VTE) in the background of HRT, i.e. deep vein thrombosis or pulmonary embolism.Therefore, when HRT is prescribed for women with risk factors for VTE, the risk-benefit ratio should be carefully weighed and discussed with the patient.
Risk factors for VTE development include individual and family history (the presence of VTE in close relatives at a relatively young age may indicate a genetic predisposition) and severe obesity. The risk of VTE also increases with age. The question of the possible role of varicose veins in the development of VTE remains controversial.
The risk of VTE may temporarily increase with prolonged immobilization, "large" planned and traumatological operations or massive trauma. Depending on the cause or duration of immobilization, it should be decided whether to temporarily discontinue HRT
It should immediately stop treatment if symptoms of thrombotic disorders occur or if they are suspected.
Arterial thromboembolism
In randomized controlled trials with long-term use of combined conjugated estrogens and medroxyprogesterone acetate, there was no evidence of a positive effect on the cardiovascular system. In large-scale clinical trials of this compound, a possible increase in the risk of coronary disease in the first year of use was found. An increased risk of stroke was also detected. To date, long-term, randomized, controlled trials have not been conducted with other HRT medications in order to detect a positive effect on morbidity and mortality related to the cardiovascular system. Therefore, it is not known whether this increased risk extends to preparations for HRT containing other types of estrogens and progestogens.
Endometrial cancer
With prolonged monotherapy with estrogens, the risk of developing hyperplasia or endometrial carcinoma increases. Studies have confirmed that the addition of gestagens reduces the risk of hyperplasia and endometrial cancer.
Mammary cancer
According to clinical trials and observational studies, an increase in the relative risk of breast cancer in women using HRT for several years has been found.This may be due to earlier diagnosis, the biological effect of HRT, or a combination of both. The relative risk increases with the duration of treatment (by 2.3 s, about a year of use ^ is possibly even greater with the combination of estrogens with progestogens, an increase comparable to the increase in the risk of breast cancer in women with each year of delay in natural menopause (by 2.8% for a year of delay), as well as obesity and alcohol abuse.The increased risk gradually decreases to the usual level during the first 5 years after the termination of HRT.
According to studies, breast cancer detected in women taking HRT is usually more differentiated than that of women who do not take it.
HRT increases the mammographic density of the mammary glands, which in some cases may have a negative impact on the radiographic detection of breast cancer.
Tumor of the liver
Against the background of the use of sex steroids, which include means for HRT, in rare cases benign, and even more rarely - malignant tumors of the liver.In some cases, these tumors led to a life-threatening intra-abdominal bleeding. With pain in the upper abdomen, enlarged liver, or signs of intra-abdominal bleeding in differential diagnosis, the probability of a liver tumor should be taken into account.
Cholelithiasis
It is known that estrogens increase the lithogenicity of bile. Some women are predisposed to the development of cholelithiasis in treatment with estrogen.
Other states
Immediately discontinue treatment, with the appearance of migraine-like or frequent and unusually severe headaches for the first time, as well as with the appearance of other symptoms-possible precursors of thrombotic cerebral stroke.
The relationship between HRT and the development of clinically significant arterial hypertension has not been established. Women taking HRT, described a small increase in blood pressure, a clinically significant increase is noted rarely. However, in some cases, with the development of HRT in the presence of a clinically significant hypertension, cancellation of HRT can be considered.
In case of mild violations of the liver function, including various forms of hyperbilirubinemia, such as Dubin-Johnson syndrome or Rotor syndrome, a doctor's supervision is necessary, as well as periodic studies of liver function. With worsening of liver function parameters HRT should be abolished.
In case of recurrence of cholestatic jaundice or cholestatic pruritus observed for the first time during pregnancy or previous treatment with sex steroid hormones, HRT should be discontinued immediately.
Special care is required for women with moderately elevated triglycerides. In such cases, the use of HRT may cause a further increase in triglyceride levels in the blood, which increases the risk of acute pancreatitis.
Although HRT may affect peripheral insulin resistance and glucose tolerance, there is usually no need to change the regimen for the treatment of diabetic patients with HRT. Nevertheless, women suffering from diabetes mellitus should be monitored during HRT.
In some patients, HRT may cause unwanted estrogen stimulation, such as abnormal uterine bleeding.Frequent or persistent abnormal uterine bleeding against the background of treatment is an indication for endometrial research.
If treatment of irregular menstrual cycles does not give results, a survey should be conducted to eliminate the organic disease.
Under the influence of estrogen, uterine fibroids may increase in size. In this case, treatment should be discontinued.
It is recommended to stop treatment with the development of recurrence of endometriosis in the background of HRT.
If you suspect a prolactinoma before starting treatment, you should exclude this disease.
In some cases, there may be a chloasma, especially in women with a history of pregnant women with chloasma. During HRT, women with a tendency to develop chloasma should avoid prolonged exposure to sunlight or ultraviolet radiation.
The following conditions may or may not occur with HRT. Although their relationship with HRT has not been proven, women with these conditions should be under the supervision of a physician when carrying out HRT: epilepsy; benign breast tumor; bronchial asthma; migraine; porphyria; otosclerosis; systemic lupus erythematosus, small chorea.
Medical examination and counseling
Before starting or resuming HRT, a woman should undergo a thorough general medical and gynecological examination (including breast examination and cytological examination of cervical mucus), and exclude pregnancy. In addition, violations of the blood coagulation system should be avoided. Periodically, follow-up examinations should be conducted.
Influence on the results of laboratory studies
Reception of sex steroids can affect the biochemical parameters of the function of the liver, thyroid, adrenal and kidney, for the transport of plasma proteins such as corticosteroid-binding globulin and lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis.